Polypeptides having protease activity, or proteases, are sometimes also designated peptidases, proteinases, peptide hydrolases, or proteolytic enzymes. Proteases may be of the exo-type that hydrolyses peptides starting at either end thereof, or of the endo-type that act internally in polypeptide chains (endopeptidases). Endopeptidases show activity on N— and C-terminally blocked peptide substrates that are relevant for the specificity of the protease in question.
The term “protease” is defined herein as an enzyme that hydrolyses peptide bonds. It includes any enzyme belonging to the EC 3.4 enzyme group (including each of the thirteen subclasses thereof). The EC number refers to Enzyme Nomenclature 1992 from NC-IUBMB, Academic Press, San Diego, Calif., including supplements 1-5 published in Eur. J. Biochem. 1997, 250, 1-6; and Eur. J. Biochem. 1999, 264, 610-650; respectively. The nomenclature is regularly supplemented and updated; see e.g. the World Wide Web (WWW) at www.chem.qmw.ac.uk/iubmb/enzyme/index.html).
US patent publication No. 2002/0182672A1 discloses, that if one or two of the last two amino acids at the C-terminus of a polypeptide is/are charged polar D or E (negatively charged) or K, R, or H (positively charged), the tail would be considered polar, charged, and this makes the polypeptide resistant against proteolytic degradation by a subclass of proteases that recognize non-polar C-terminal tails of secreted proteins.
Another disclosure reported, that proline residues at the C-terminus of nascent polypeptide chains induce degradation of the polypeptide (2002. Prolin residues at the C terminus of nascent chains induce SsrA tagging during translation termination. J. Biol. Chem. 277:33825-33823).